Halides, aryl, arylation rearrangement

To be really satisfactory, a Friedel-Crafts alkylation requires one relatively stable secondary or tertiary carbocation to be formed from the alkyl halide by interaction with the Lewis acid, i.e. cases where there is not going to be any chance of rearrangement. Note also that we are unable to generate carboca-tions from an aryl halide - aryl cations (also vinyl cations, see Section 8.1.3) are unfavourable - so that we cannot nse the Friedel-Crafts reaction to join aromatic gronps. There is also one further difficulty, as we shall see below. This is the fact that introduction of an alkyl substitnent on to an aromatic ring activates the ring towards fnrther electrophilic substitution. The result is that the initial product from Friedel-Crafts alkylations is more reactive than the... 

Limitations of FC alkylation FC alkylations are hmited to alkyl halides. Aryl or vinyl halides do not react. FC alkylation does not occur on aromatic rings containing strong electron-withdrawing substituents, e.g. —NO, —CN, —CHO, —COR, —NH, —NHR or —NR group. Multiple substitutions often take place. Carhocation rearrangements may occur, which result in multiple products. 

However, displacement reactions of this type differ from the previously discussed displacements of activated aryl halides in that rearrangement often occurs. That is, the entering group does not always occupy the same position on the ring as that vacated by the halogen substituent. For example, the hydrolysis of 4-chloromethylbenzene at 340° gives an equimolar mixture of 3- and 4-methylbenzenols ... 

In suitable vinylic halides, nucleophilic photosubstitution occurs intramolecular- 295-297,324,330-332 por jnstance irradiation of 113 in methanol only yields benzofuran 114, and no vinyl ether product or 1,2-aryl rearrangement products are formed (equation 84a)296. Apparently, the reaction with an internal nucleophile is faster than the 1,2-aryl shift and also faster than the reaction with an external nucleophile. With the less stabilized vinyl cations derived from the a-methyl- and a-H-analogues of 113-OMe, 1,2-aryl shifts do... 

The synthetic applicability is rather limited, due to the various side-reactions observed, such as eliminations and rearrangement reactions. The attempted coupling of two different alkyl halides in order to obtain an unsymmetrical hydrocarbon, usually gives the desired product in only low yield. However the coupling reaction of an aryl halide with an alkyl halide upon treatment with a metal (the Wurtz-Fittig reaction) often proceeds with high yield. The coupling of two aryl halides usually does not occur under those conditions (see however below ) since the aryl halides are less reactive. 

Symmetrical ketones can be prepared in good yields by the reaction of organo-mercuric halides with dicobalt octacarbonyl in THF, or with nickel carbonyl in DMF or certain other solvents. The R group may be aryl or alkyl. However, when R is alkyl, rearrangements may intervene in the C02(CO)g reaction, though the Ni(CO)4 reaction seems to be free from such rearrangements. Divinylic ketones... 

Partitioning of carbocations between addition of nucleophiles and deprotonation, 35, 67 Perchloro-organic chemistry structure, spectroscopy and reaction pathways, 25, 267 Permutations isomerization of pentavalent phosphorus compounds, 9, 25 Phase-transfer catalysis by quaternary ammonium salts, 15, 267 Phenylnitrenes, Kinetics and spectroscopy of substituted, 36, 255 Phosphate esters, mechanism and catalysis of nucleophilic substitution in, 25, 99 Phosphorus compounds, pentavalent, turnstile rearrangement and pseudoration in permutational isomerization, 9, 25 Photochemistry, of aryl halides and related compounds, 20, 191 Photochemistry, of carbonium ions, 9, 129... 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

S)-(-)-CITRONELLOL from geraniol. An asymmetrically catalyzed Diels-Alder reaction is used to prepare (1 R)-1,3,4-TRIMETHYL-3-C YCLOHEXENE-1 -CARBOXALDEHYDE with an (acyloxy)borane complex derived from L-(+)-tartaric acid as the catalyst. A high-yield procedure for the rearrangement of epoxides to carbonyl compounds catalyzed by METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE) is demonstrated with a preparation of DIPHENYL-ACETALDEHYDE from stilbene oxide. A palladium/copper catalyst system is used to prepare (Z)-2-BROMO-5-(TRIMETHYLSILYL)-2-PENTEN-4-YNOIC ACID ETHYL ESTER. The coupling of vinyl and aryl halides with acetylenes is a powerful carbon-carbon bond-forming reaction, particularly valuable for the construction of such enyne systems. 

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